[Transcapillary filtration of plasma proteins in patients with diabetes type II microangiopathy complications].

This study presents the results of the research on transcapillary filtration of plasma proteins in patients with non-insulin dependent diabetes mellitus (NIDDM). The aims of the study were as follows: (a) Examination of transcapillary filtration of plasma proteins in patients with NIDDM; (b) Search for correlations between metabolic status of diabetes, severity of diabetic microangiopathy and penetration of individual protein fractions into the blister fluid; (c) Examination of the influence of nonenzymatic glycation on albumin fragmentation and its transcapillary filtration. It was also decided to check whether changes in the blister fluid would appear earlier than fundal fluorescein angiography or microalbuminuria, two markers of diabetic microangiopathy. The study enrolled 34 patients with type II diabetes mellitus, aged 35-78 years, with a mean disease duration of 12.5 years (SD = 7.8). The control group included 10 non-diabetic volunteers aged 31-76 years. The mean age in both groups did not differ significantly. The cantharidin blister method was used to study the permeability of capillary vessels. The following laboratory tests were done: concentrations of serum urea, creatinine, glucose, fructosamine, glycated hemoglobin, cholesterol, and triglycerides. Electrophoretic separation of proteins in plasma and blister fluid was performed and the concentration of fructosamine in fluid was measured. Routine urinalysis was supplemented with microalbuminuria. The eye fundus was inspected and fundal fluorescein angiography was done. The influence of nonenzymatic glycation on protein fragmentation and its possible impact on the permeability of capillary vessels was determined with in vitro glycation of human serum albumin. In patients without diabetic retinopathy the Cb:Cs ratio for beta-globulin turned out to be significantly lower than in patients with proliferative retinopathy. Patients with normoalbuminuria had the Cb:Cs ratio for alpha 2-globulin significantly lower than patients with urinary albumin concentrations > or = 165 mg/L. When the group was divided with regard to serum fructosamine concentrations, the subgroup with fructosamine concentrations lower than 3 mmol/L revealed a significantly higher Cb:Cs ratio for fructosamine than the subgroup with fructosamine > or = 3 mmol/L. Concentrations of total protein, albumin, beta-globulin and gamma-globulin in blister fluid correlated positively with glycemia in the control group. Blister fluid concentration of beta-globulin correlated positively with HbAIC concentration. In the study group, total protein content in blister fluid correlated negatively with duration of diabetes and level of glycosuria. Concentrations of blister fluid alpha 1-globulin and gamma-globulin correlated negatively with glycosuria. Concentrations of blister fluid beta-globulin correlated negatively with duration of diabetes. Electrophoretic separation of in vitro SDS glycosylated human serum revealed no additional fraction in the incubated samples. Electrophoretic separation of in vitro glycosylated albumin disclosed co-migration of albumin monomers incubated for varying times with glucose.

CONCLUSIONS

1. Glycation of human serum and albumin does not cause fragmentation of the proteins, but decreases transcapillary filtration of albumin due to change of molecular electric charge. 2. Patients with non-insulin dependent diabetes and microangiopathic complications reveal increased transcapillary transport of alpha 2- and beta-globulin in skin. 3. Increased permeability of skin capillary vessels for alpha 2- and beta-globulin in diabetic microangiopathy reflects an advanced stage of the disease and may facilitate progression.